For example, the rat ribosomal protein S3a is identical to the product of the rat v-fos transformation effector gene . And S3a is normally involved in initiation of protein synthesis and is related to proteins involved in the regulation of growth and the cell mTOR inhibitor cycle . In one study, over expression of S3a was able to induce transformation of NIH 3T3 cells and induce formation of tumors in nude mice . But the ability of S3a to induce transformation was dependent on its role in suppressing RG7112 programmed cell death . A second example is the rat ribosomal protein L10. L10 is homologous to a DNA-binding protein
and to a putative Wilm’s tumor suppressor gene . A third example is S19 where a mutation in the S19 ribosomal protein has been associated with a predisposition to cancer in patients with Diamond-Blackfan anaemia . Finally, RPS2 was shown by our lab to specifically bind a classical ‘break point cluster region’ sequence found
in leukemia , implicating RPS2 as a DNA binding protein. The DNA binding domain is a leucine zipper Y-27632 manufacturer domain where 4 point mutations have been detected. Thus, aberrant over expression of RPS2 or the mutant form of RPS2 (termed PCADM-1) might somehow activate oncogenes involved in tumor development. In this connection, the individual and/or combined effects of a variety of ribosomal proteins (i.e. like RPS2, S3a, L10, and L19) might directly control gene expression patterns, oncogene expression and transformation. Conclusion We believe that Aspartate targeting one or more of these ribosomal proteins (i.e. RPS2 or S3a) may lead to development of a highly effective treatment for prevention
of cancer, eradication or primary tumors or a blockade of tumor metastasis. Acknowledgements We thank Drs. Robert Bright and Susan Topalian, National Cancer Institute, NIH, Bethesda MD; who kindly provide cell lines of CPTX-1532 and NPTX-1532. We thank Donna Peehl (Stanford Univ.) for the gift of BPH-1 cells. Supported by a grant to mes: CA76993. Electronic supplementary material Additional file 1: Illustrates the basic design of the DNAZYM-1P construct. Shows 8b flanking regions which correspond to specific sequences in the 5′ region of the RPS2 mRNA. The 15 b core of the DNAZYM-1P constitutes the catalytic domain, the ’10-23′ motif . (PDF 13 KB) References 1. Ohkia A, Hu Y, Wang M, Garcia FU, Stearns ME: Evidence for a Prostate Cancer Associated Diagnostic Marker-1, PCADM-1: Immunohistochemistry and In situ hybridization studies. Clin Can Res 2004, 10: 2452–58.CrossRef 2. Vaarala MH, Porvari KS, Kyllonen AP, Mustonen MV, Lukkarinen O, Vihko PT: Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: Confirmation of L7a and L37 over-expression in prostate cancer tissue samples. Int J Cancer 1998, 78: 27–32.CrossRefPubMed 3.